A US cost-effectiveness study has suggested that very early intervention with disease-modifying anti-rheumatic drugs (DMARD) is cost-effective in patients with recently diagnosed rheumatoid arthritis (RA); it is uncertain whether very early therapy with biologic agents is cost-effective.

There is increasing evidence that early aggressive treatment in patients with RA is associated with improved outcomes and possibly an increased chance of long-term remission or control. Early aggressive therapy has disadvantages, however, for example increased certainly in diagnosis is required to minimise the risk of patients being exposed to aggressive and costly treatment unnecessarily. It is also not clear which is the most cost-effective strategy.

The authors of this study used current data to examine the cost-effectiveness of different treatment strategies in patients with very early RA (symptom duration <3 months). They used an individual sampling model to track the course of disease over time in hypothetical patient cohorts. While five strategies were initially investigated, the authors concentrate on the three most plausible clinically: the pyramid strategy (initial treatment with NSAID, mechanical methods, and low-dose corticosteroids, with DMARD at one year in non-responders); an early DMARD strategy, in which conventional DMARD (e.g. leflunomide, sulphasalazine, hydroxychloroquine, or methotrexate) are given within 12 weeks of symptom onset; and thirdly, an early biologic strategy (very early use of biologics, defined as use of 3 sequential tumour necrosis factor inhibitors, in combination with methotrexate). Patient characteristics and all costs used US data; indirect costs related to patients’ inability to work were included. Outcome was cost per QALY gained, and the incremental cost effectiveness ratio (ICER) was used to compare the strategies.

According to the base case analysis, both early aggressive treatment strategies delayed progressive joint damage, thus influencing costs of care and QALY compared to the pyramid strategy. Over a lifetime, the DMARD strategy gives a gain in QALY compared to the pyramid strategy, and in this model the additional costs were nearly offset by the gains from reductions in healthcare use (ICER $4,849 per QALY; 95% CI, $0 to $16,354 per QALY). When indirect costs were included, the cost savings increase and the early DMARD strategy dominates (i.e. is cheaper than) the pyramid strategy.

Using current biologic agents, the early biologic strategy offered most benefits for the first ten years, however it was less effective over a lifetime because patients were assumed to move to DMARD therapy which at that point would be less effective. This strategy only retained its benefits if it was assumed that there would always be an effective biologic agent available, and this came at a significant cost (ICER $157,350 per QALY; 95% CI, $98,540 to $194,256 per QALY compared with the early DMARD strategy).

Overall, the early DMARD strategy seemed to dominate the early biologic strategy: it maximised the effectiveness of early DMARD and reserved biologics for those with greater treatment resistance of longer duration, for whom the incremental benefit is greater.

In sensitivity analyses, early biologics become more cost-effective if drug prices are reduced, risk for death is permanently lowered through biologic therapy, patients experience drug-free remission, responders can be selected before therapy initiation, or effective alternative agents are available for patients for whom several biologics have failed. Their costs still remain high, however – in the best-case scenario, the ICER for this strategy fell as low as $46,900 compared with the early DMARD strategy.

The authors conclude that in their model, early aggressive treatment of RA with DMARD may be a cost-effective option, given the future healthcare costs that may be saved. When indirect costs associated with lost productivity were included, this option became cost saving. Early use of biologics was most effective providing the assumption that there would always be an effective agent holds true, however this comes at significantly greater cost. They caution that their results should be interpreted carefully as there are limited data on long-term outcomes, and note that they have identified areas where further research is required.

[Editor’s note: as this analysis used US data, its results cannot be extrapolated directly to other healthcare systems; they may, however, be indicative.]